The major goal of this proposal is to elucidate for the first time the mode of action of a teratogen at the molecular level in both animal models and humans with congenital abnormalities. The abnormality to be studied is glucocorticoid-induced cleft palate in rodents. The hypothesis to be tested is that the teratogenic action of glucocorticoids is mediated by an H-2 regulated cytosolic receptor, and involves inhibition of arachidonic acid release and prostaglandin synthesis, shelf elevation, and medial edge epithelial breakdown. This grant will investigate the role of glucocorticoids in each of these steps of they hypothesized teratogenic mechanism.